Biomedical subjects

P Deloron

Publications and source records attributed to P Deloron.

At least 37 records · Page 2Linked to original sources

PubMed1999

Longitudinal study of Plasmodium falciparum infection and immune responses in infants with or without the sickle cell trait.

BACKGROUND: Individuals may be homozygous (SS) or heterozygous (AS) sickle cell gene carriers or have normal adult haemoglobin (AA). Haemoglobin S could have a protective role against malaria but evidence is sparse and the operating mechanisms are poorly known. METHODS: We followed two cohorts of children. The first was enrolled at birth (156 newborn babies) and the second at 24-36 months old (84 children). Both cohorts were followed for 30 months; monthly for parasitological data and half yearly for immunological data. RESULTS: In the first cohort, 22%, and in the second 13% of children were AS. Whatever their age parasite prevalence rates were similar in AA and AS individuals. Mean parasite densities increased less rapidly with age in AS than in AA children, and were significantly lower in AS than in AA children >48 months old. The AA children tended to be more often admitted to hospital than AS children (22% versus 11%, NS). Both anti-Plasmodium falciparum and anti-Pfl55/RESA antibody rates increased more rapidly in AA than in AS children. Conversely, the prevalence rate of cellular responders to the Pfl55/RESA antigen was similar in AA and AS children during the first 2 years of life, then it was higher in AS than in AA children. CONCLUSIONS: Sickle cell trait related antimalarial protection varies with age. The role of the modifications of the specific immune response to P. falciparum in explaining the protection of AS children against malaria is discussed.

Animals↗

PubMed1999

Development of antibodies against chondroitin sulfate A-adherent Plasmodium falciparum in pregnant women.

In areas where Plasmodium falciparum is endemic, pregnant women are at increased risk for malaria, and this risk is greatest during the first pregnancy. The placenta sequesters parasites that are able to cytoadhere to chondroitin sulfate A (CSA), a molecule expressed by the placental syncytiotrophoblast, while parasites from a nonpregnant host do not bind to CSA. Cytoadherence is mediated by the expression of variants of the P. falciparum-erythrocyte membrane protein 1 family. Each member of this molecule family induces antibodies that specifically agglutinate infected erythrocytes and inhibit their cytoadherence ability. We investigated whether the higher susceptibility of primigravidae was related to the lack of immune response towards CSA-binding parasites. In a cross-sectional study, primigravidae delivering with a noninfected placenta were less likely to have antibodies agglutinating CSA-binding parasites than multigravidae (P < 0.01). In contrast, parasites from nonpregnant hosts were as likely to be recognized by the sera from women of various parities. In a longitudinal study, at 6 months of pregnancy, antibodies against CSA-binding parasites were present in 31.8% of primigravidae and in 76.9% of secundigravidae (P = 0.02). The antibodies against CSA-binding parasites inhibited the cytoadherence of a CSA-adherent parasite strain to the human placental trophoblast. Our data support the idea that the higher susceptibility of primiparae is related to a lack of a specific immune response to placental parasites.

Adhesiveness↗

PubMed1999

Immune responses against Plasmodium falciparum asexual blood-stage antigens and disease susceptibility in Gabonese and Cameroonian children.

The frequency and level of cellular and humoral responses to seven synthetic peptides from asexual blood stages of Plasmodium falciparum were measured in two cohorts of children living in areas highly endemic for malaria in Gabon and Cameroon. A prospective longitudinal study was conducted for one year in these sites to examine the relationship between specific in vitro immune responses and susceptibility to clinical malaria. Clinical protection was related to high proliferative responses (merozoite surface antigen-1 [MSA-1] and MSA-2 peptides) as well as to elevated antibody levels (schizont extract, MSA-2, and rhoptry-associated protein-1 [RAP-1] peptides) in the village of Dienga, Gabon. Higher response rates of interferon-gamma but lower response rates of tumor necrosis factor-alpha to four and six peptides, respectively, were observed in Dienga than in Pouma that were independent of the older age of the Gabonese children. Age accounted only for the higher prevalence rate in Dienga of the antibody responders to the peptide from Pf155/ring-infected erythrocyte surface antigen (RESA). Our results support the inclusion of epitopes from MSA-1, MSA-2, RAP-1, and Pf155/RESA antigens in a subunit vaccine against malaria, but show that a longitudinal clinical, parasitologic, and immunologic study conducted according to identical criteria in two separate areas may lead to contrasting observations, demonstrating the geographic limitation of the interpretation of such results.

Adolescent↗

PubMed1999

Factors influencing resistance to reinfection with Plasmodium falciparum.

A treatment-reinfection study design was used to investigate the relationships between host immunologic and/or genetic factors and resistance to reinfection with Plasmodium falciparum. Sixty-one children in Gabon were enrolled in a cross-sectional study to measure the prevalence of each human plasmodial species. All were given amodiaquine for radical cure of parasites, and 40 were subsequently followed-up for 30 weeks. Successive blood smears were examined to measure the delay of reappearance in blood of asexual stages of P. falciparum parasites. Presence of infection during the cross-sectional survey was associated with male sex, non-deficient glucose-6-phosphate dehydrogenase activity, plasma interleukin-10 level, and anti-LSA-Rep antibody concentration. Resistance to reinfection was related to the presence of anti-LSA-J antibodies, and the absence of anti-LSA-Rep antibodies. Moreover, P. malariae-infected subjects were usually co-infected with P. falciparum, and were also more rapidly reinfected with P. falciparum after treatment, compared with those without P. malariae infection.

Adolescent↗

PubMed1999

Use of polymerase chain reaction for accurate follow-up of Loa loa experimental infection in Mandrillus sphinx.

Mandrills (Mandrillus sphinx) experimentally infected with human Loa loa usually remain microfilaremic for a long period of time. Nevertheless some control their microfilaremia while still harboring adults worms, and therefore become occult-infected. A nested polymerase chain reaction (PCR) assay, targeted on the repeat 3 region of the gene coding for the L. loa 15-kD protein (15r3-PCR), has been evaluated in mandrills infected with third-stage larvae (L3) of L. loa. The results of this assay were negative during the prepatency period (4 months after inoculation), but became positive when microfilariae appeared in the blood, and remained positive in all mandrills, even in those that became amicrofilaremic. These results show that the positivity of the 15r3-PCR assay is linked to the appearance of microfilariae in peripheral blood and demonstrated that L. loa-specific DNA can be detected in blood from occult-infected mandrills.

Animals↗

PubMed1999

Relationships between malaria prevalence and malaria-related morbidity in school children from two villages in central Africa.

To investigate the relationship between parasite prevalence and malaria-related morbidity, we carried out a comparative study among cohorts of school children from two villages, Dienga, Gabon, and Pouma, Cameroon, both located in malaria-endemic areas. Seven to 17 year-old children attending primary schools were similarly followed-up at each site to evaluate the frequency of malaria attacks. Follow-up involved daily temperature recording (and blood smears in the case of fever) and preparation of blood smears every two weeks. In Pouma, 186 children were followed-up for six months. In Dienga, 228 children were followed-up for nine months. The mean prevalence rate of Plasmodium falciparum infections (as assessed by the blood smears) was twice as high in Pouma compared with Dienga (45.2% versus 26.8%; P < 0.0001), whereas the monthly malaria attack rate (as assessed by the daily surveillance) was twice as high in Dienga compared with Pouma (21.5% versus 41.4%; P = 0.003). The possible implication of several parameters that may differ between the two areas, such as the malaria transmission level, the economical and social status of the inhabitants, the characteristics of infecting parasite strains, and the genetic background of the population, is discussed.

Adolescent↗

PubMed1999

[Comparative analysis of 2 diagnostic methods of human loiasis: IgG4 serology and nested PCR].

By evaluating the diagnostic methods developed in our laboratory, the prevalence of loaiosis was estimated among 201 individuals from the province of Haut Ogooué in Gabon using IgG4 serology and nested-PCR. The study showed that the prevalence of loaiosis was higher than that described using standard microscopy. IgG4-based ELISA (Enzyme Linked Immunosorbant Assay) using crude extract of Loa loa microfilariae showed that 80% (35/44) of microfilaraemic individuals (MF') and 56% (88/157) of amicrofilaraemics (AMF) presented antibodies. By contrast, L. loa specific DNA amplified by nested-PCR was detected in all MF and in 68% (106/157) of AMF. Among the 201 samples tested, 95 (47%) gave positive results in both tests. These results indicate that the presence of IgG4 antibodies directed against crude extract of L. loa microfilariae is not linked to the positivity of nested-PCR assay (chi 2 for paired data = 8.78; P < 0.02). We conclude that the PCR assay is more sensitive than the detection of IgG4 antibodies (directed against crude extract of L. loa microfilariae) in detecting loaiosis, and particularly occult loaiosis (infection without circulating microfilariae).

Animals↗

PubMed1999

[Relationship between the intensity of Loa loa filariasis transmission and prevalence of infections].

Filarial loiasis differs from other filariases in that most infected subjects are amicrofilaremic. This difference raises the notion of occult infection. The aim of this study was to evaluate the relationship between the intensity of transmission and incidence of infection. For this purpose we determined the incidence of loiasis both microscopically and by PCR in 201 subjects from three villages in the province of Haut Ogooue in Gabon. Intensity of transmission, expressed in ATP (annual transmission potential) in these villages was estimated to be 250 infecting larvae per individual per year (L3/man/yr) in Moyabi, 180 L3/man/yr in N'dokaye, and 43,000 L3/man/yr in Okoumbi. Although there was no significant difference between the three villages with regard to the incidence of microfilaremia (21 p. 100 and 22 p. 100), the incidence of occult infection, i.e., positive PCR in amicrofilaremic subjects, was 45 p. 100 in Moyabi, 79 p. 100 in N'dokaye and 80 p. 100 in Okoumbi. The overall incidence of loiasis was 57 p. 100 in Moyabi and 85 p. 100 in both N'dokaye and Okoumbi. These findings demonstrate that the incidence of loiasis is correlated with the intensity of transmission (p < 0.001), especially in children. Taking this information into account will improve control of Loa loa in endemic areas.

Adolescent↗

PubMed1998

Plasmodium falciparum-isolates from Cameroonian pregnant women do not rosette.

The placenta of pregnant women is frequently parasitized by erythrocytes infected by mature stages of Plasmodium falciparum (IE), a phenomenon associated with low birth weight of the offspring. The cytoadherence phenotype of the parasites from pregnant women suggests that placental sequestration may result from cytoadherence to the syncytiotrophoblast. However, as anatomopathological studies report that cytoadherence in the placenta is a rare event, we investigated whether placental parasites may sequester by forming rosettes with uninfected erythrocytes, another possible sequestration mechanism. Parasites from placental blood as well as parasites from the peripheral blood of pregnant and non pregnant subjects were assessed for their ability to rosette. In non pregnant subjects, the rosetting capacity of parasites was as reported in literature while, except in one case, parasites from pregnant women did not rosette. We conclude that the lack of rosetting is a new feature of IEs from pregnant women and that rosetting cannot be involved in the placental sequestration of IEs.

Adolescent↗

PubMed1998

Effect of chloroquine prophylaxis during pregnancy on maternal haematocrit.

Two controlled trials of chloroquine prophylaxis during pregnancy were performed, one in Burkina Faso in 1987, on all pregnant women, and the other in Cameroon in 1992, on primigravidae only. Maternal haematocrit at delivery was found to be significantly higher in those women who had received chloroquine than in those who had not, both in Burkina Faso (37.4% v. 36.5%; P = 0.01) and in Cameroon (34.8% v. 32.8%; P = 0.02). Anaemia, defined as an haematocrit of < 30%, was also less common in those treated with chloroquine (6.3% v. 8.5% in Burkina Faso and 8.3% v. 18.4% in Cameroon) but this difference was not significant in either country. A slight improvement in haematological status when prophylaxis is given has also been observed in similar studies performed in other tropical countries. The present results confirm the usefulness of targeting antimalarial prophylaxis at pregnant women. Such prophylaxis during the first pregnancy also increases birthweight.

Anemia↗

PubMed1998

An in vitro microassay to assess the ability of Plasmodium falciparum-infected erythrocytes to bind to the human syncytiotrophoblast.

PROBLEM: Erythrocytes parasitized by matures stages of Plasmodium falciparum are frequently sequestered in human placenta. The consequences of this sequestration have been well described, but little is known about the mechanisms used by the parasite to concentrate in the placenta. METHOD OF STUDY: We developed an in vitro assay to study their binding capacity to the human syncytiotrophoblast. Our cytoadherence test was scaled down, and each step of the assay was optimized to enhance the sensitivity of our model. RESULTS: Cytoadherence assays between P. falciparum-infected erythrocytes and human trophoblasts are easily performed using low numbers of trophoblast cells. The process can also be used to carry out immunofluorescence and immunostaining techniques. CONCLUSIONS: The test may be adapted to any kind of cell, is inexpensive, and allows the culture of virtually any kind of cell for several weeks.

Animals↗

PubMed1998

Prevalence of and risk factors for anemia in young children in southern Cameroon.

Anemia during childhood remains a major public health challenge in sub-Saharan Africa. To determine the prevalence of and the main risk factors for anemia in young children, we conducted a longitudinal survey in Ebolowa in southern Cameroon. Children were enrolled in two cohorts and followed during a three-year period: the first cohort was composed of 122 children from 0 to 36 months of age and the second cohort was composed of 84 children from 24 to 60 months of age. The two cohorts were followed weekly for symptomatic malaria, monthly for both symptomatic and asymptomatic malaria, and every six months for hematologic data; the children were grouped into six-month age groups. The prevalence of anemia (hemoglobin [Hb] level < 11 g/dl) was the highest in the six-month-old age group (47%) and the age-related evolution clearly showed a decrease in the prevalence from three years of age. Thus, 42% of the children less than three years of age were anemic, while 21% of the children between three and five years of age were anemic. The lowest mean +/- SD Hb content (10.7 +/- 2.1 g/dl) was observed in the six-month-old children and a regular improvement in the Hb level occurred from six months to three years of age. A stabilization was observed at a level of approximately 12 g/dl. At any age, there was no difference in mean Hb levels between children with AS and AA Hb genotypes. Hookworm infection was diagnosed in two children in the study population. Results of a multivariate analysis showed that placental malaria infection was the strongest risk factor for anemia in the six-month-old children (odds ratio [OR] = 3.6; 95% confidence interval [CI] = 1.1-12.3) and was independent of the frequency of parasitemia, parasitemia at the time of Hb measurement, or microcytosis. In the one-year-old age group, microcytosis was a significant factor related to anemia (OR = 2.8, 95% CI = 1-7.8) pointing out the role of iron deficiency at this age. Parasitemia at the time of Hb measurement was significantly associated with anemia in all age groups (except in 54- and 60-month-old groups). Strategies to decrease the prevalence of anemia in young children in southern Cameroon should include chemoprophylaxis for pregnant women, prevention of acquired malaria infection in both pregnancy and infancy, and prevention of nutritional iron deficiency.

Anemia↗

PubMed1998

Parasite antigen-specific interleukin-10 and antibody reponses predict accelerated parasite clearance in Plasmodium falciparum malaria.

Using strict inclusion criteria, we conducted a hospital-based, case-control study in which 100 Gabonese children with severe Plasmodium falciparum malaria were matched for age, gender and provenance with 100 children presenting with mild malaria. Parasite antigen-specific cellular and humoral immunological responses were measured and compared with post-treatment parasite clearance times in each group. Significantly faster parasite clearance times were associated with in vitro production of IL-10 by acute-phase peripheral blood mononuclear cells (PBMC) in response to both liver and asexual stage parasite antigens, but not with proliferative, IFN-gamma, or TNF responses to the same antigens. In addition, in those children with mild malaria, higher levels of acute-phase antibody responses to liver stage antigen-1 (LSA-1) were associated with faster parasite clearance times, and were correlated with the presence of IL-10 responses to the same antigen. No such associations were found for IL-10 or antibody responses to a range of asexual blood stage antigens. Those with severe malaria had significantly lower levels of anti-LSA-1 antibodies compared to their counterparts with mild malaria. In conclusion, the results of this study suggest that parasite antigen-specific IL-10-mediated antibody responses may play a role in the control of asexual stage parasite multiplication in P. falciparum malaria.

Amino Acid Sequence↗

PubMed1997

Maternal placental infection with Plasmodium falciparum and malaria morbidity during the first 2 years of life.

In areas endemic for malaria, pregnant women frequently present with a placenta that has been parasitized by Plasmodium falciparum, an infection associated with a reduction in the birth weight of the offspring. However, the impact of placental infection on malaria-related morbidity during the infant's first years of life has not been investigated. Between 1993 and 1995, 197 children in southern Cameroon were followed weekly clinically and monthly parasitologically. The dates of first positive blood smear and the evolution of the parasite prevalence rates were compared between infants born to mothers presenting with (n = 42) and without (n = 155) P. falciparum infection of the placenta. Infants born to placenta-infected mothers were more likely to develop a malaria infection between 4 and 6 months of age; then the difference progressively disappeared. Similarly, parasite prevalence rates were higher in placenta-infected infants from 5 to 8 months of age. Thus, malarial infection of the placenta seems to result in a higher susceptibility of infants to the parasite. This was not related to maternally transmitted antibodies, as specific antibody levels were similar in both groups of infants. A better understanding of the involved mechanisms may have important implications for the development of malaria control strategies.

Animals↗

PubMed1997

Purification of Pf155/RESA antigen from supernatants of in vitro Plasmodium falciparum cultures by continuous elution electrophoresis.

The malaria parasite Plasmodium falciparum synthesizes a protein, Pf155/RESA, which associates with the membrane of newly invaded erythrocytes. Using spent supernatants from P. falciparum growing in culture as a source of soluble Pf155/RESA, we have developed a purification technique based on the concentration of these supernatants, followed by gel filtration and continuous elution electrophoresis. SDS-PAGE electrophoresis and immunoblots were used to establish the quality of the purification.

Animals↗

PubMed1997

Immune response to Plasmodium falciparum antigens in Cameroonian primigravidae: evolution after delivery and during second pregnancy.

Mechanisms responsible for the increase in malaria susceptibility during pregnancy, and in particular during the first pregnancy, have not been elucidated. T and B cell responses to leucoagglutinin, bacille Calmette-Guerin (BCG) and to six Plasmodium falciparum antigens were longitudinally investigated in 33 pregnant women during their first pregnancy, after delivery, and during second pregnancy. Parasitological data obtained from the same women during and after the first pregnancy demonstrated the higher risk of P. falciparum infection during this pregnancy. Plasma levels of antibodies to Pf155/ RESA were lower during pregnancy than after delivery. Conversely, antibodies to P. falciparum asexual blood stages were higher during pregnancy than after delivery, suggesting that during pregnancy the regulation of antibody production may be variously impaired depending upon the antigens. The most striking finding of the present study is the impairment of the IL-2 cellular response during the first pregnancy. Conversely, proliferative responses, as well as IL-4 and interferon-gamma (IFN-gamma) responses, were either unaffected or moderately enhanced. No difference in humoral and cellular responses was observed between first and second pregnancy. The impairment of the IL-2 responses involved the response to malaria peptides and proteins, as well as the response to non-malarial antigens and to the mitogen leucoagglutinin. Thus, the alteration of malaria immunity might rather fall into the general frame of the depression of cellular immunity during pregnancy than involve a specific malaria phenomenon.

Amino Acid Sequence↗

PubMed1997

Therapeutic efficacy of clindamycin in combination with quinine for treating uncomplicated malaria in a village dispensary in Gabon.

The efficacy of a 3-day clindamycin-quinine regimen to treat clinical malaria attacks was investigated in 256 children from western Gabon. Treatment was well tolerated by all of the children and its efficacy was higher than 97% by day 20. Thus this 3-day clindamycin-quinine regimen might constitute a potential alternative to chloroquine for treating clinical malarial attacks in children from Gabon.

Adolescent↗

PubMed1997

Isotypic analysis of maternally transmitted Plasmodium falciparum-specific antibodies in Cameroon, and relationship with risk of P. falciparum infection.

In malaria-endemic areas, infants are relatively protected against malaria infection. Such protection is though to be related principally to the transplacental transfer of maternal antibodies. We measured total and Plasmodium falciparum-specific IgG (including subclasses), IgM, and IgE antibodies in 154 paired maternal-cord serum samples from an area of meso- to hyperendemic malaria in South Cameroon. Among peripheral mother blood samples, total IgG and IgM were detected in all samples, IgE in all but two. Plasmodium falciparum-specific IgG were detected in all serum samples, IgM and IgE in > 75% of samples. The prevalence rates of anti-P. falciparum IgG subclasses varied from 75% to 97%. With the exception of P. falciparum-specific IgG, all antibody class and subclass levels were lower in cord blood than in peripheral mother blood. Plasmodium falciparum-specific IgG1 and IgG3 isotypes were transferred to the offspring more often and more efficiently than IgG2 and IgG4. The detection of total and P. falciparum-specific IgM and IgE in some cord serum samples demonstrated that fetuses can mount humoral response against malaria parasites. We also determined whether transplacentally acquired antibodies protect against malaria infection by relating the antibody levels at birth to the risk of acquiring P. falciparum infection during the first 6 months of life. Among various classes and subclasses of P. falciparum-specific antibodies, only IgG2 were related to a decrease in the risk of acquiring a P. falciparum peripheral blood infection from birth to 6 months of age.

Adolescent↗